1. Field of the Invention
This invention relates to a diagnostic method for stroke.
2. Description of the Related Art
Stroke has the third highest death-rate in industrial countries. It is caused either by bleeding in the brain from a ruptured blood vessel (haemorrhagic stroke) or by obstruction of a blood vessel in the brain (ischaemic or thrombotic stroke). Stroke results from either a permanent or a transient reduction in cerebral blood flow. This reduction in flow is, in most cases, caused by the arterial occlusion due to either an embolus or a local thrombosis. Depending on the localisation of brain injury and the intensity of necrosed neurones, stroke symptoms can become a life handicap for patients and the death rate from stroke events approaches 30%.
Recently, S100B was described as a potential biochemical marker for stroke diagnosis, see U. Missler et al., “S100 protein and neuron-specific enolase concentrations in blood as indicators of infarct volume and prognosis in acute ischemia stroke”, Stroke 1997; 28:1956-60. However, S100B has also been reported as a useful marker for early detection of metastases of melanoma and cerebral complications from head injury and cardiac surgery. Thus, the sensitivity and specificity of the S100B test were limited to 44% and 67%, respectively, see M. Takahashi et al., “Rapid and sensitive immunoassay for the measurement of serum S100B using isoform-specific monoclonal antibody”, Clin. Chem. 1999; 45:1307-11. Development of new stroke markers would help clinicians to establish early diagnosis.
WO 01/42793 relates to a diagnostic assay for stroke in which the concentration of heart or brain fatty acid binding protein (H-FABP or B-FABP) is determined in a sample of body fluid.
U.S. Pat. No. 6,225,047 describes the use of retentate chromatography to generate difference maps, and in particular a method of identifying analytes that are differentially present between two samples. One specific method described therein is laser desorption mass spectrometry.
WO 01/25791 describes a method for aiding a prostate cancer diagnosis, which comprises determining a test amount of a polypeptide marker, which is differentially present in samples of a prostate cancer patient and a subject who does not have prostate cancer. The marker may be determined using mass spectrometry, and preferably laser desorption mass spectrometry.
Development of new non-invasive stroke markers for body fluids and new methods of determining the markers would help clinicians to establish early diagnosis. This problem has now been solved by the present invention.
Our earlier application PCT/EP03/01462 (WO 03/069346) discloses a method of diagnosis of stroke or the possibility thereof in a subject suspected of suffering from stroke, which comprises subjecting a sample of body fluid taken from the subject to mass spectrometry, thereby to determine a test amount of a polypeptide in the sample, wherein the polypeptide is differentially contained in the body fluid of stroke-affected subjects and non-stroke-affected subjects, and has a molecular weight in the range of from 3000 to 30000; and determining whether the test amount is consistent with a diagnosis of stroke. In a preferred embodiment the mass spectrometry involves surface-enhanced laser desorption/ionisation (SELDI).